Exploration of the cytotoxic and microtubule disruption potential of novel imidazo[1,5-]pyridine-based chalcones.

In continuation of our efforts to develop new anticancer compounds, a new series of imidazo[1,5-]pyridine-chalcone derivatives was designed, synthesized, characterized, and evaluated for its cytotoxicity against five human cancer cell lines, , breast (MDA-MB-231), colon (RKO), bone (Mg-63), prostate (PC-3), and liver (HepG2) cell lines, as well as a normal cell line (HEK). Among the synthesized compounds, two exhibited promising cytotoxicity against the MDA-MB-231 cell line with IC values of 4.23 ± 0.

A dipyridophenazine Ni(II) dithiolene complex as a dual-acting cancer phototherapy agent activatable within the phototherapeutic window.

A combination of photodynamic therapy (PDT) and photothermal therapy (PTT) within the phototherapeutic window (600-900 nm) can lead to significantly enhanced therapeutic outcomes, surpassing the efficacy observed with PDT or PTT alone in cancer phototherapy. Herein, we report a novel small-molecule mixed-ligand Ni(II)-dithiolene complex (Ni-TDD) with a dipyridophenazine ligand, demonstrating potent red-light PDT and significant near-infrared (NIR) light mild-temperature PTT activity against cancer cells and 3D multicellular tumour spheroids (MCTSs). The four-coordinate square planar complex exhibited a moderately intense absorption band (ε ∼ 3700 Mcm) centered around 900 nm and demonstrated excellent dark and photostability in an aqueous phase.

Exploration of mercaptoacetamide-linked pyrimidine-1,3,4-oxadiazole derivatives as DNA intercalative topo II inhibitors: Cytotoxicity and apoptosis induction.

The design and synthesis of a new series of mercaptoacetamide-linked pyrimidine-1,3,4-oxadiazole hybrids was accomplished. The in vitro cytotoxic potential of these new compounds was evaluated against lung cancer (A549), prostate cancer (PC-3, DU-145) and human embryonic kidney (HEK) cell lines. Compound 9p showed the highest potency on A549 cells with an IC value of 3.

Co-encapsulated nanoparticles of Erlotinib and Quercetin for targeting lung cancer through nuclear EGFR and PI3K/AKT inhibition.

Erlotinib-based EGFR targeted therapy has proven significant clinical improvement against non-small cell lung cancer (NSCLC). However, the anticancer activity of Erlotinib (Ertb) is limited by the development of Ertb resistance and possess a challenge to clinicians and patients. To explore a better therapeutic strategy, we evaluated Ertb in combinations with different natural products.

Synthesis and biological evaluation of novel imidazo[1,2-a]pyridine-oxadiazole hybrids as anti-proliferative agents: Study of microtubule polymerization inhibition and DNA binding.

Efforts towards the development of potential anticancer agents, a new series of imidazo[1,2-a]pyridine-oxadiazole hybrids were synthesized and evaluated for their in vitro anticancer activity against lung cancer (A549) and prostate cancer (PC-3, DU-145) cell lines. Amongst the compounds tested, 6d showed the highest potency on A549 cells with an IC value of 2.8 ± 0.

Design and synthesis of substituted (1-(benzyl)-1-1,2,3-triazol-4-yl)(piperazin-1-yl)methanone conjugates: study on their apoptosis inducing ability and tubulin polymerization inhibition.

A library of substituted (1-(benzyl)-1-1,2,3-triazol-4-yl)(piperazin-1-yl)methanone derivatives were designed, synthesized and screened for their cytotoxic activity against BT-474, HeLa, MCF-7, NCI-H460 and HaCaT cells by employing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Among all the synthesized analogues, compound displayed the highest cytotoxicity with the IC value of 0.99 ± 0.

New imidazo[2,1-]thiazole-based aryl hydrazones: unravelling their synthesis and antiproliferative and apoptosis-inducing potential.

Herein, we have designed and synthesized new imidazo[2,1-]thiazole-based aryl hydrazones () and evaluated their anti-proliferative potential against a panel of human cancer cell lines. Among the synthesized compounds, and elicited promising cytotoxicity against the breast cancer cell line MDA-MB-231 with IC values of 1.65 and 1.

Novel diindoloazepinone derivatives as DNA minor groove binding agents with selective topoisomerase I inhibition: Design, synthesis, biological evaluation and docking studies.

We present here-in the molecular design and chemical synthesis of a novel series of diindoloazepinone derivatives as DNA minor groove binding agents with selective topoisomerase I inhibition. The in vitro cytotoxicity of the synthesized compounds was evaluated against four human cancer cell lines including DU143, HEPG2, RKO and A549 in addition to non-cancerous immortalized human embryonic kidney cells (HEK-293). Compound 11 showed significant cytotoxicity against all the four human cancer cell lines with IC values ranging from 4.

Discovery of certain benzyl/phenethyl thiazolidinone-indole hybrids as potential anti-proliferative agents: Synthesis, molecular modeling and tubulin polymerization inhibition study.

A series of certain benzyl/phenethyl thiazolidinone-indole hybrids were synthesized for the study of anti-proliferative activity against A549, NCI-H460 (lung cancer), MDA-MB-231 (breast cancer), HCT-29 and HCT-15 (colon cancer) cell lines by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). We found that compound G37 displayed highest cytotoxicity with IC value of 0.92 ± 0.

A Comprehensive Review on the Therapeutic Versatility of Imidazo [2,1-b]thiazoles.

Background: Imidazo[2,1-b]thiazole, a well-known fused five-membered hetrocycle is one of the most promising and versatile moieties in the area of medicinal chemistry. Derivatives of imidazo[2,1-b]thiazole have been investigated for the development of new derivatives that exhibit diverse pharmacological activities. This fused heterocycle is also a part of a number of therapeutic agents.

Design, synthesis, and antimicrobial evaluation of 1,4-dihydroindeno[1,2-]pyrazole tethered carbohydrazide hybrids: exploring their ADMET, ergosterol inhibition and ROS inducing potential.

A series of new 1,4-dihydroindeno[1,2-]pyrazole tethered carbohydrazide hybrids () were designed, synthesized and evaluated for their antimicrobial activity. Compounds , , , and demonstrated significant activity against the entire panel of test pathogens. Further, compounds and exhibited significant anti- activity.

Nimbolide protects against endotoxin-induced acute respiratory distress syndrome by inhibiting TNF-α mediated NF-κB and HDAC-3 nuclear translocation.

Acute respiratory distress syndrome (ARDS) is characterized by an excessive acute inflammatory response in lung parenchyma, which ultimately leads to refractory hypoxemia. One of the earliest abnormalities seen in lung injury is the elevated levels of inflammatory cytokines, among them, the soluble tumor necrosis factor (TNF-α) has a key role, which exerts cytotoxicity in epithelial and endothelial cells thus exacerbates edema. The bacterial lipopolysaccharide (LPS) was used both in vitro (RAW 264.

LC/QTOF/MS/MS characterization, molecular docking and in silico toxicity prediction studies on degradation products of anagliptin.

Pharmaceutical drugs are potential molecules with specific biological activity. However, long-term use of these chemical molecules can affect the human physiological system because of their increased levels in the human body. Therefore, identification and structure elucidation of impurities or degradation products should be taken into consideration in order to assure drug safety.

Synthesis, molecular modeling and evaluation of α-glucosidase inhibition activity of 3,4-dihydroxy piperidines.

Biological evaluation of 3,4-dihydroxy piperidines as α-glucosidase inhibitors is being reported for the first time. Forty-five derivatives (amides, di-amides and sulfonamides) were made using cis and trans 3,4-dihydroxy piperidines to evaluate their α-glucosidase inhibition activity. Polar groups (-OH, -NH) on phenyl ring having derivatives 5i, 5l, 7g, 7i &12j showed excellent activity compared to standard references.

Curcumin inspired 2-chloro/phenoxy quinoline analogues: Synthesis and biological evaluation as potential anticancer agents.

Synthesis of twenty new curcumin inspired 2-chloro/phenoxy quinoline derivatives is outlined in this study. The obtained new chemical entities were screened in vitro for their cytotoxic activity towards various tumor cell lines. Of the compounds screened, 6c and 9d exhibited significant activity and the most active analogue 6c displayed promising cytotoxicity against PC-3 (IC of 3.

Synthesis and biological evaluation of longanlactone analogues as neurotrophic agents.

Longanlactone analogues were synthesized using a route featuring Friedel-Crafts acylation, Sonogashira coupling and 1,3-dipolar cycloaddition reactions. Structure-activity relationships were investigated for neurotrophic activity. Compound 6 was found to have the most potent neurotrophic activity among all the synthesized analogues in Neuro2a cells as evidenced by a battery of in vitro/cell based assays for assessment of neurogenic and potential neurotrophic activity including neurite outgrowth assay and real time PCR for popular markers of augmented neurotrophic activity.

Glycogen synthase kinase-3 and its inhibitors: Potential target for various therapeutic conditions.

Glycogen Synthase Kinase-3 (GSK-3) is a serine/threonine kinase which is ubiquitously expressed and is regarded as a regulator for various cellular events and signalling pathways. It exists in two isoforms, GSK-3α and GSK-3β and can phosphorylate a wide range of substrates. Aberrancy in the GSK-3 activity can lead to various diseases like Alzheimer's, diabetes, cancer, neurodegeneration etc.

Synthesis and biological evaluation of curcumin inspired imidazo[1,2-a]pyridine analogues as tubulin polymerization inhibitors.

With an aim to develop new curcumin inspired analogues as potent anticancer agents, we synthesized a series of (1E,4E)-1-phenyl-5-(3-phenylimidazo[1,2-a]pyridin-2-yl)penta-1,4-dien-3-ones (12a-t) as tubulin polymerization inhibitors. An initial screening was carried out to evaluate their cytotoxic potential on a panel of six cancer cell lines namely, cervical (HeLa), gastric (HGC-27), lung (NCI-H460), prostate (DU-145 and PC-3) and breast (4T1), using MTT assay. Among the compounds tested, compounds 12e, 12r and 12t showed potent growth inhibition and 12t {(1E,4E)-1-(3-(3,4-difluorophenyl)imidazo[1,2-a]pyridin-2-yl)-5-(2,4,6-trimethoxyphenyl)penta-1,4-dien-3-one} being the most active member of the series inhibited the growth of all the tested cell lines with IC values varying from 1.

Structure based design, synthesis and activity studies of small hybrid molecules as HDAC and G9a dual inhibitors.

Aberrant enzymatic activities or expression profiles of epigenetic regulations are therapeutic targets for cancers. Among these, histone 3 lysine 9 methylation (H3K9Me2) and global de-acetylation on histone proteins are associated with multiple cancer phenotypes including leukemia, prostatic carcinoma, hepatocellular carcinoma and pulmonary carcinoma. Here, we report the discovery of the first small molecule capable of acting as a dual inhibitor targeting both G9a and HDAC.

Telomerase Inhibition and Human Telomeric G-Quadruplex DNA Stabilization by a β-Carboline-Benzimidazole Derivative at Low Concentrations.

Guanine rich regions in DNA, which can form highly stable secondary structures, namely, G-quadruplex or G4 DNA structures, affect DNA replication and transcription. Molecules that stabilize G4 DNA have become important in recent years. In this study, G4 DNA stabilization, inhibition of telomerase, and anticancer activity of synthetic β-carboline-benzimidazole derivatives (5a, 5d, 5h, and 5r) were studied.

Synthesis of thiazole linked indolyl-3-glyoxylamide derivatives as tubulin polymerization inhibitors.

A series of thiazole linked indolyl-3-glyoxylamide derivatives were synthesized and evaluated for their in vitro cytotoxic activity against DU145 (prostate), PC-3 (prostate), A549 (lung) and HCT-15 (colon) cancer cell lines by employing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Among all the synthesized compounds, compound 13d displayed cytotoxicity of IC = 93 nM towards DU145 cancer cell line. The most active compound 13d was also tested on RWPE-1 cells and was found to be safe compared to the DU145 cells.

Synthesis, molecular modeling and biological evaluation of aza-flavanones as α-glucosidase inhibitors.

An efficient acid catalyzed methodology has been employed to synthesize a variety of aza-flavanones and their α-glucosidase inhibitory activity is evaluated using acarbose, miglitol and voglibose as reference standards. Molecular modeling studies were performed for all compounds to identify the important binding modes responsible for the inhibition activity of α-glucosidase which helped find key interactions between the enzyme and the active compounds. Among all the compounds , and have shown high α-glucosidase inhibition activity compared to standard reference drugs and have been identified as promising potential antidiabetic agents.

Synthesis and α-glucosidase inhibition activity of dihydroxy pyrrolidines.

A new series of Deacetylsarmentamide A and B derivatives, amides and sulfonamides of 3,4-dihydroxypyrrolidines as α-glucosidase inhibitors were designed and synthesized. The biological screening test against α-glucosidase showed that some of these compounds have the positive inhibitory activity against α-glucosidase. Saturated aliphatic amides were more potent than the olefinic amides.

Synthesis of C-tethered indolyl-3-glyoxylamide derivatives as tubulin polymerization inhibitors.

A series of C-tethered Indolyl-3-glyoxylamide derivatives were synthesized and evaluated for their in vitro cytotoxic activity against DU145 (prostate), PC-3 (prostate), A549 (lung) and HCT-15 (colon) cancer cell lines by employing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Among all the synthesized compounds, compound 7f displayed cytotoxicity of IC = 140 nM towards DU145 cancer cell line. The treatment of DU145 cells with 7f led to inhibition of cell migration ability.